Behavioral Memory Modulation in Nicotine Addiction

Targeting Foundational Memory Processes in Nicotine Addiction: A Translational Clinical Neuroscience Study of a Retrieval-Extinction Intervention to Reduce Craving and Smoking Behavior

The purpose of the study is to see if a behavioral intervention known as retrieval-extinction training (RET) might affect craving in response to nicotine cues (e.g., pictures, videos and objects) and smoking behavior in men and women who smoke cigarettes.

Study Overview

• Status: Completed
• Conditions: Nicotine Use Disorder
• Intervention / Treatment: Behavioral: Retrieval Extinction Training (RET); Behavioral: Control Retrieval Extinction Training (RET)

Detailed Description

In a recently published NIDA-funded study, the investigators found that lasting reductions in craving and smoking could be achieved with a brief behavioral intervention designed to alter memory processes underlying smoking-related nicotine addiction. The proposed project will replicate and extend these findings by 1) increasing the dose of intervention so as to bolster the observed treatment effects, 2) employing brain imaging methods to identify patterns of brain activity uniquely associated with the intervention and potentially predictive of treatment outcome, 3) extending follow-up period to more completely document the long-term effects of the intervention. Positive findings from this study could lead to the development of brief therapy that will not only improve treatment outcomes for smokers, but also be used in the treatment other substance use disorders and frequently co-occurring comorbidities such as PTSD.

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

1. Healthy men and women, ages 25 to 65, who have smoked at least 10 cigarettes per day for at least 3 years.
2. Participants must live within a 50-mile radius of the research facility and have reliable transportation.
3. Participants must be willing to abstain from smoking starting the night before the baseline visit, and starting the night before visit 1 and remain abstinent for four consecutive days.
4. Participants must agree to forego any other medication or behavioral treatment for smoking cessation while enrolled in the study (with the exception of the SC Quitline).

Exclusion Criteria

1. Participants who are dependent on substances other than nicotine.
2. Women who are pregnant during the clinical assessment session or either of the fMRI sessions. These participants must agree to notify the study staff if they become pregnant during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: R-E (Retrieval Extinction); 83 anticipated participants will undergo 3 sessions on consecutive days of the Retrieval Extinction Training (RET) intervention consisting of a 5-minute 'retrieval' smoking-content video followed 10 minutes later by 1 hour of 'extinction' training consisting of four sequences of smoking-related cues (e.g., pictures). Participants will also receive a lab-based smoking-related cue-reactivity experience during the baseline assessment and 24-hour follow-up test.	Behavioral: Retrieval Extinction Training (RET); Retrieval extinction training (RET) is a behavioral intervention that involves cue-elicited retrieval followed by extinction training (i.e., massed unreinforced exposure to drug-associated cues). The first element of RET involves briefly presenting drug-associated cues to retrieve drug use memories. The second element, occurring after a brief interval, involves extinction training. It is argued that the initial retrieval of the memories prior to extinction training initiates a period of instability, which is followed by reconsolidation of the memories back into long-term storage. Extinction training during the period of instability is presumed to overwrite the original drug-associated cue with a non-drug-associated cue, to attenuate expression of drug-seeking behavior.
Other: NR-E (No R-E); 83 anticipated participants will undergo 3 sessions on consecutive days of the control Retrieval Extinction Training (RET) intervention consisting of a 5-minute 'retrieval' non-smoking or neutral-content video followed 10 minutes later by 1 hour of 'extinction' training consisting of four sequences of non-smoking or neutral cues (e.g., pictures). Participants will also receive a lab-based non-smoking or neutral cue-reactivity experience during the baseline assessment and 24-hour follow-up test.	Behavioral: Control Retrieval Extinction Training (RET); The control retrieval extinction training (RET) for the NR-E arms serves as the control intervention to the RET behavioral intervention. The first element of the control RET involves briefly presenting retrieval cues that contain neutral, non-smoking content. The second element, occurring after a brief interval, involves extinction training. Based on findings from the previous NIDA-funded R21, the R-E arm reported a significant 25 percent reduction in cigarettes smoked per day during the follow-up period versus the control NR-E arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Craving Questionnaire Score, Response to the Novel Cue	At each visit (baseline, intervention sessions, and follow-up test sessions), participants will complete a Craving Questionnaire survey at multiple timepoints during each visit (baseline, and after each cue exposure). The craving questionnaire is the average of four statements about craving for cigarettes (e.g., "I have an urge for a cigarette"), and the participants rate how they agree with the statements at that moment on a scale of 1 to 5 (1 = strongly disagree and 5 = strongly agree). This measure will examine the behavioral response to the novel cue over the course of the study, and differences in response between the R-E arms and NR-E arms.	up to 24 weeks, Baseline, 24 hours, Weeks 2, 4, 6, 8, 12, and 24
Mean Cigarettes Smoked Per Day	Cigarettes Smoked per Day were recorded daily and summarized at follow-up visits	up to 26 weeks, Baseline, Weeks 2, 4, 6, 8, 12, 16, 21 and 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Smoking Days	Cigarettes Smoking days were recorded daily and summarized at follow-up visits. The percentage of days since last follow up visit where smoking is recorded is reported	up to 26 weeks, Baseline, Weeks 2, 4, 6, 8, 12, 16, 21 and 26
Mean Mood-Craving Response to the Novel Cue	At each visit (baseline, intervention sessions, and follow-up test sessions), participants will complete a mood craving during each visit. The mood craving form is a single item question ranging from 0 (no craving) to 100 (greatest craving possible). This measure will examine the behavioral response to the novel cue over the course of the study, and differences in response between the R-E arms and NR-E arms.	up to 24 weeks, Baseline, 24 Hours, Weeks 2, 4, 6, 8, 12, and 24

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Drug Abuse (NIDA); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Michael Saladin, PhD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2019
• Primary Completion (Actual): October 28, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: November 13, 2018
• First Submitted That Met QC Criteria: November 13, 2018
• First Posted (Actual): November 16, 2018

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Tobacco Use Disorder
• Other Study ID Numbers: 00069355; R01DA043587 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No